Materials and methods for engineering cells and uses thereof in immuno-oncology
AssigneeCrispr Therapeutics AG
InventorsJonathan Alexander Terrett, Demetrios Kalaitzidis, Lawrence Klein
Life of this patent
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Abstract
Materials and methods for producing genome-edited cells engineered to express a chimeric antigen receptor (CAR) construct on the cell surface, and materials and methods for genome editing to modulate the expression, function, or activity of one or more immuno-oncology related genes in a cell, and materials and methods for treating a patient using the genome-edited engineered cells.
Claims29
A population of cells comprising engineered human T cells, wherein the engineered human T cells comprise:
- (a) a disrupted T cell receptor alpha chain constant region (TRAC) gene comprising a deletion of the nucleotide sequence of SEQ ID NO:
- 76;
- (b) a nucleic acid comprising a nucleotide sequence encoding a chimeric antigen receptor (CAR) comprising (i) an ectodomain that comprises an anti-BCMA single-chain variable fragment (scFv), wherein the anti-BCMA scFv comprises a variable heavy chain comprising the amino acid sequence of SEQ ID NO:
- 1524, 1530, or 1589, and a variable light chain comprising the amino acid sequence of SEQ ID NO:
- 1526, 1527, 1531, or 1590, (ii) a CD8 transmembrane domain, and (iii) an endodomain that comprises a CD28 or 41BB co-stimulatory domain and a CD3z co-stimulatory domain, and wherein the nucleic acid is inserted in the disrupted TRAC gene;
- and
- (c) a disrupted beta-2-microglobulin (B2M) gene.
A population of cells comprising engineered human T cells, wherein the engineered human T cells comprise:
- (a) a disrupted TRAC gene comprising a deletion of the nucleotide sequence of SEQ ID NO:
- 76;
- (b) a nucleic acid comprising a nucleotide sequence encoding a CAR comprising (i) an ectodomain that comprises an anti-BCMA scFv, wherein the anti-BCMA scFv comprises the amino acid sequence of SEQ ID NO:
- 1503, 1504, 1505, 1506, 1509, 1511, 1513, or 1514, (ii) a CD8 transmembrane domain, and (iii) an endodomain that comprises a CD28 or 41BB co-stimulatory domain and a CD3z co-stimulatory domain, and wherein the nucleic acid is inserted in the disrupted TRAC gene;
- and
- (c) a disrupted B2M gene.
A population of cells comprising engineered human T cells, wherein the engineered human T cells comprise:
- (a) a disrupted TRAC gene comprising a deletion of the nucleotide sequence of SEQ ID NO:
- 76;
- (b) a nucleic acid comprising a nucleotide sequence encoding a CAR, wherein the CAR comprises the amino acid sequence of SEQ ID NO:
- 1453, 1454, 1455, 1456, 1457, 1460, 1461, 1463, 1465, or 1466, and wherein the nucleic acid is inserted in the disrupted TRAC gene;
- and
- (c) a disrupted B2M gene.
Dependencies are inferred from the claim text.